SUMMARY OF WORK Vascular smooth muscle cells (VSMCs) play a major role in the arterial wall response to injury. VSMCs are normally present in the arterial tunica media where they regulate vascular tone and blood flow. In the vessel wall, VSMCs are surrounded and separated from other cells by extracellular matrix (ECM). Vascular injury leads to proliferation of medical VSMCs and migration of these cells from the media to the intima. These steps are dependent on the local degradation and remodeling of the ECM. Previous studies in the rat model of carotid artery injury showed that infection VSMCs with adenovirus-mediated tissue inhibitor of metalloproteinase (AdCMV.hTIMP-2) caused a significant reduction in VSMC migration within 4 days after injury and in neointimal formation 8 days after injury as compared to VSMC infected with AdCMV.null. In addition, AdCMV.hTIMP-2 was previously shown no effect on cell proliferation in cultured VSMC. Therefore, experiments were aimed at elucidating the long-term effect of AdCMV.hTIMP-2 on neointimal formation in the rat of carotid artery injury. In this study, 6 month old rats underwent balloon injury of the common carotid artery. The vessel wall was infected either with AdCMV.hTIMP-2 or with the control vector AdCMV.null at time of balloon injury. At 21 days post injury and infection, there was a 12% inhibition in neointimal formation between AdCMV.hTIMP-2 and AdCMV.null infected carotid arteries which were not statistically significant. Medial area was similar in the two groups. These results indicate that Ad-mediated TIMP-2 over expression in the rat model of carotid artery injury inhibits VSMC migration which leads to a significant decrease neointimal formation at the early phase (within 7 days after injury) of neointimal development. However, VSMCs migration occurring between 7 days and 21 days is relatively insignificant compared to neointimal VSMC proliferation, so inhibition of VSMC migration has no effect on overall neointimal thickness. Furthermore, these results suggest that unless neointimal VSMC proliferation can be reduced or blocked, it appears unlikely that neointimal thickness will be reduced.